Hydrogen Bromide → HCID 13553298, compound

Participants

Reaction Conditions

Reaction Steps

A 5 1, 3-necked round-bottom flask, equipped with an overhead stirrer, thermometer and addition funnel was charged with 2-bromo-4,6-dimethylaniline hydrobromide (713 g, 2.54 mol) and acetone (1.9 1). The slurry was cooled to 15° C. and 48% aqueous hydrobromic acid (450 ml, 4.0 mol), was added. The mixture was cooled to -4° C. then a solution of sodium nitrite (219 g, 3.17 mol) in 400 ml of water was slowly added with vigorous stirring while maintaining an internal temperature of 0° C. Acrylonitrile (550 ml) was charged and the reaction mixture was degassed under vacuum then purged with nitrogen. Cuprous bromide (3.0 g, 0.021 mol) was charged and the mixture stirred with gradual warming to ambient temperature over 6 hours. The mixture was aged with stirring, for 6 additional hours. The mixture was concentrated under vacuum, collecting 3 1 of solvent. The residue was diluted with toluene (3 1), the organic extract was washed with 3×500 ml of water, dried over sodium sulfate, filtered, and concentrated to a volume of 1 1. The dark concentrate was charged with triethylamine (1.2 1) and heated at 80°-90° C. under nitrogen for 6.5 hours. The mixture was concentrated under vacuum to a thick slurry then diluted with toluene (2.5 1). The organic phase was extracted 2×500 ml with 3 N aqueous hydrochloric acid, 2×500 ml with water, then dried over sodium sulfate. After filtration the toluene extract was treated with activated charcoal (10 g) at ambient temperature then filtered through super-cel. Removal of the solvent in vacuo yielded a yellow oil which solidified on standing. The crude nitrile was dissolved in a solution of cyclohexane (525 ml) and hexanes (840 ml) with heating. The mixture was gradually cooled to 3° C., filtered, washed with 500 ml of cold hexane and dried in vacuo to yield the Compound 2a as a light yellow solid (mp 95°-96° C.). The crystallization mother liquors contained an additional product.

Provenance & Evidence